The long-term goals of this research are to examine the deleterious effects of cocaine on the circulation. There has been mass media coverage of fatal cardiovascular failure of major sports players and stars, however, the actual sequence of events that result in death has not been well documented. Death has usually been attributed to cerebral incident or heart failure. However, cocaine is known to have action on arterial resistance and also acts in the central nervous system and periphery affecting norepinephrine transmission of neural impulses. The principal short-term regulator of blood pressure-the carotid sinus baroreceptors-also controls the cardiovascular system via norepinephrine pathways. Therefore, the potential for significant alterations in vascular control exists. This can be of particular importance when any physical or emotional stresses such as exercise are introduced to a system modified by cocaine. Alterations in baroreceptor function may cause an inability to normally compensate for the physiological stresses. The specific goals of this study are to quantitatively document cocaine's effect on cardiac output, arterial resistance, and other vascular properties over time, and to examine the extent of the baroreceptor alterations in neural control of the circulation. Adjustments in the gain if the carotid baroreceptors will be investigated in anesthetized dogs which have had the carotid sinus baroreceptors isolated and then cocaine administered. To study vascular properties, namely, vascular capacity, animals will be placed on cardiopulmonary constant-flow bypass and blood volume changes will be followed to determine venous capacity, venous compliance, and changes in arterial pressure and resistance without changes in cardiac output or heart parameters. Finally, similar parameters will be studied in conscious animals over several weeks to evaluate short-term repeated administration of cocaine and to study the effects without anesthesia and acute surgical trauma.